EPSTEIN-BARR VIRUS IN HODGKIN'S DISEASE

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This Small Grant project will expand an ongoing, NCI-funded, epidemiologic case-control study of Hodgkin's disease (HD) in San Francisco-Bay Area women by collecting and incorporating data on Epstein-Barr virus (EBV) in tumor cells of case subjects. EBV recently has been implicated as a pathogenetic cofactor in about one-half of HD tumors. As HD thus may be subclassifiable as EBV-positive and EBV-negative, addition of EBV data to the ongoing study will enhance its primary investigation of reproductive risk factors by providing more precise disease endpoints, i.e., HD subgroups defined by EBV status. The aims of this Small Grant project are: 1) to collect archived tumor specimens from case subjects in the ongoing study, apply standard molecular virologic techniques to identify EBV latent gene products in HD tumor cells, and classify each case subject as EBV-positive or EBV-negative; 2) to determine if reproductive risks, e.g., a protective effect of parity, differ for women with EBV-positive and EBV- negative HD; 3) to describe the distribution of EBV-positive and EBV- negative HD by age, race, and histologic subtype, and explore risks for the two virus-defined subgroups associated with various additional factors being measured, including social class characteristics that increase HD risk. The ongoing study ultimately will involve 315 women with HD and 315 population controls in in-person interviews covering demographic, reproductive, hormone-use, social class, familial, medical, and other lifestyle topics. Diagnosis and histologic classification of HD are being reviewed for accuracy. To date, 96% of invited case subjects have been interviewed. For the Small Grant project, we will request interviewed subjects' tumor tissue specimens from pathologists; in a pilot study, we have acquired specimens for about 85% of subjects. Access to tumor specimens is time- limited, as it is based on signed consent from subjects to release pathologic materials for the ongoing study, soon to be completed. Specimens will be mailed to our coinvestigator, who will test sections for EBV latent gene products using polymerase chain reaction, EBER in situ hybridization, and immunoperoxidase techniques to detect LMP-1, with positive and negative controls. This hybridization method is sensitive, consistent, rapid, and produces no cellular or other herpesvirus cross- hybridization. Data analysis will characterize EBV-positive and EBV- negative HD by variables presently under investigation, using descriptive statistics. Multivariate statistical methods will estimate and compare odds ratios for EBV-positive and EBV-negative HD associated with reproductive and other risk factors, after adjustment for suspected confounders. As one of the first studies to combine molecular virologic and extensive personal risk factor data in a population-based series of HD cases, this Small Grant project will provide initial epidemiologic evaluation of EBV-positive and EBV-negative HD by a variety of characteristics postulated and established to increase risk of this lymphoma.